tbuckley/cabot-search huggingface dataset:
AB0285 MANAGEMENT OF ATLANTO-AXIAL SUBLUXATION IN RHEUMATOID ARTHRITIS PATIENTS
Authors: S. Miladi, S. Bouzid, A. Fazaa, H. Boussaa, M. Yasmine, K. Ouenniche, S. Kassab, C. Selma, K. Ben Abdelghani, A. Laatar
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Recent studies have shown that around 86% of Rheumatoid Arthritis (RA) have cervical spine involvement [1]. The synovial inflammation in the upper cervical spine causes instability. Atlanto-axial subluxation (AAS) is the most frequent injury of the cervical spine in RA. <h3>Objectives</h3> Our study aimed to assess the medical management of AAS in our RA patients. <h3>Methods</h3> We conducted a retrospective, monocentric study, including patients fulfilling the ACR/EULAR 2010 criteria for RA. All patients had a confirmed AAS on MRI of the cervical spine findings. Disease activity was assessed using the disease activity score 28 (DAS-28). Treatment received by each patient, before and after the occurrence of AAS, was noted. <h3>Results</h3> We included 19 patients with a confirmed AAS. The mean age was 62±14.91 years. Male to female ratio was 0.5. The mean disease duration was 19.27±8.04 years. RA was erosive in all patients and immunopositive in 87% (n=13). When AAS occurred, twelve patients were on csDMARDS. The mean DAS28 ESR was 5.25±1.1. According to DAS28ESR, high disease activity was noted in 10 patients (66.7%). Methotrexate was the most frequent treatment used (n=9, 60%). An association of Methotrexate and sulfasalazine was prescribed in 5 cases (33%). Two patients were using leflunomide. Three patients were on bDMARDS. Nine patients (60%) received bolus steroid therapy. These patients had a vascularized synovial pannus on MRI findings. Four patients remained on the same DMARDs. An association of sulfasalazine to methotrexate was performed in 6 patients. A change from csDMARDs to bDAMRDs was undergone in only two patients (from sulfasalazine to rituximab, and from leflunomide to etanercept). A switch of bDMARDs was performed in three patients: from infliximab to rituximab in one case, and from rituximab to tocilizumab in two others. Surgical treatment was indicated in three patients for neurological complications, but the patients did not agree to proceed with the surgery. <h3>Conclusion</h3> AAS is a potentially lethal complication of RA. The use of bolus steroid therapy can be handy to reduce acute inflammation. However, adjustment of DMARDs is needed to better control RA activity and to slow its progression. <h3>Reference</h3> [1] Shlobin, N.A., Dahdaleh, N.S. Cervical spine manifestations of rheumatoid arthritis: a review. Neurosurg Rev 44, 1957–1965 (2021). <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.
AB0096 INVESTIGATION OF THE EFFECTS OF KYNURENIC ACID ANALOG IN ANKYLOSING SPONDYLITIS AND PSORIATIC ARTHRITIS
Authors: B. Varga, F. Fülöp, G. Toldi, L. Vécsei, Y. Mándi, A. Balog
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> The anti-inflammatory and immunosuppressive functions of kynurenic acid (KYNA) is in the center of attention. Previously, we demonstrated the effects of KYNA analog on the blood samples of rheumatoid arthritis patients <i>in vitro.</i> The results showed the suppression of tumor necrosis factor-α (TNF-α), S100A12 (EN-RAGE), S100A8/9 (calprotectin) and α-defensin production, with the increase of tumor necrosis factor-stimulated gene-6 protein (TSG-6) levels. <h3>Objectives</h3> In the present study, we compared the effects of the previously used newly synthetized KYNA analog on the TNF-α, S100A8/9, S100A12 alarmins, α-defensin and interleukin-17 (IL-17) production, correlation with the effects on the TSG-6 expression in ankylosing spondylitis (AS) and psoriatic arthritis (PsA). <h3>Methods</h3> 38 PsA and 54 AS patients were involved and divided in subgroups based on disease activity. Heat inactivated <i>Staphylococcus aureus</i> (SA1) were used as cytokine inducers on peripheral blood mononuclear cells (PBMC) isolated from blood samples of healthy controls, and patients. In parallel <i>in vitro</i> experiments, the SA1 induced PBMCs were pretreated with the KYNA analog. The concentrations of the above mentioned inflammatory mediators in the supernatants were quantified by ELISA. <h3>Results</h3> The SA1 induced the TNF-α, TSG-6, calprotectin and α-defensin production while only a modest increase could be seen in the concentration of EN-RAGE, and had no effect on the IL-17 levels. KYNA analog attenuated the SA1 induced TNF-α, calprotectin and α-defensin production, and increased the TSG-6 production. Addition of KYNA analog had no effect on the EN-RAGE and IL-17-levels. The cytokine inducer effect of SA-1 was the mildest in the blood samples of patients with csDMARD or NSAID therapy. The TNF-α inhibitory effect of the KYNA analog correlated inversely with the TSG-6 stimulatory effect. <h3>Conclusion</h3> TSG-6 expression could participate in the suppression of inflammatory cytokines, such as TNF-α, calprotectin and α-defensin in spondylarthropathies. The elevation of the TSG-6 production by KYNA analog is a possible mechanism behind the antiinflammatory effect of KYNA, marking it a potential target for therapeutic application in the treatment of immune mediated diseases such as AS, PsA or RA. <h3>REFERENCES:</h3> NIL. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.
POS1224 CLINICAL FEATURES AND PREDICTORS OF MYOCARDIAL INVOLVEMENT IN ANTI-SYNTHETASE SYNDROME PATIENTS
Authors: C. Campochiaro, G. De Luca, M. B. Cilona, G. Mancuso, L. Dagna
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Anti-synthetase syndrome (ASS) is a rare systemic connective tissue disease with protean clinical manifestations. Myocarditis is one of the most worrisome organ involvement<sup>[1]</sup>. <h3>Objectives</h3> To investigate the features associated with myocardial involvement and the predictors of myocarditis in ASS patients. <h3>Methods</h3> ASS patients followed up at our Myositis Clinic were identified. Patients were classified as having myocarditis whether they had a positive cardiac magnetic resonance (CMR) and/or a positive endomyocardial biopsy (EMB). All patients underwent troponin T, NTproBNP and echocardiography at first evaluation at our centre. Those with palpitations and/or evidence of arrhythmias also underwent 24-hour Holter-ECG. Patients with abnormalities in one the above mentioned parameters underwent CMR +/- EMB. The presenting features and the prevalence of traditional cardiovascular risk factors were compared between the 2 groups. Univariate and multivariate logistic regression analyses were performed. <h3>Results</h3> 43 ASS patients were identified, 13 (30%) with myocarditis and 30 (70%) without myocarditis; of these baseline echocardiography data and troponin T and NTproBNP levels before immunosuppressive treatment introduction were available for all myocarditis patients and for 22 ASS patients without myocarditis. The clinical characteristics of patients are summarized in Table 1. At baseline myocarditis patients were more frequently male, had more raised levels of troponin T (although not always with values &gt; 5 times upper limits of normality), NTproBNP, liver enzymes and CRP. Of note, for what concerns clinical features, only fever was more frequently observed in ASS patients with myocarditis (69% versus 17%, p = 0.001). At multivariate logistic regression analysis only the presence of fever at baseline (OR 7.707, 95%CI 1.026 – 57.917, p =0.047) was associated with myocarditis. <h3>Conclusion</h3> Myocarditis is not a rare, but likely, an overlooked manifestation in ASS. Myocarditis in ASS can be subtle as shown by the presence of only slightly raised cardiac enzymes in some patients and the absence of striking echocardiographic or clinical features. The presence of fever might suggest that a more inflammatory phenotype is associated with myocarditis in ASS. <h3>Reference</h3> [1]Dieval C. Myocarditis in Patients With Antisynthetase Syndrome: Prevalence, Presentation, and Outcomes. Medicine 2015. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.
AB0063 OSTEOCLASTS DIFFERENTIATED FROM DENDRITIC CELLS POSSESS THE INFLAMMATORY OSTEOCLAST PHENOTYPE
Authors: T. Mizuno, Y. Matsueda, K. Yamaoka
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Osteoclasts (OCs) can differentiate from monocytes (MoOC) and dendritic cells (DCOC) in in vitro. On the other hand, there are two OC subsets in in vivo. One is involved in normal bone remodeling, and the other originating from arthirits-associated osteoclastogenic macrophages (AtoM), characterized by CX3CR1 and FOXM1 expression. However, the relationship between MoOC and DCOC with AtoM is unknown[1]. <h3>Objectives</h3> To investigate the phenotype of oteoclasts differentiated from dendritic cells. <h3>Methods</h3> Bone marrow cells or bone marrow derived dendritic cells were cultured with RANKL+M-CSF for 6 days to generate MoOC or DCOC.(2) Osteoclast differentiation was assessed by TRAP staining. NFATc1, CX3CR1 and FOXM1 mRNA expression was evaluated with whole cultured cells, OC or undifferentiated cells residing by OC collected by laser microdissection. Fluorescent immunostaining of cultured cells was used to analyze protein expression, and IL-6 or TNFα was added during OC differentiation to assess effects on OC differentiation, CX3CR1 and FOXM1 expression. <h3>Results</h3> MoOCs and DCOCs differentiation was confirmed by TRAP staining and NFATc1 mRNA expression in whole cultured cells on day 6 of RANKL+M-CSF culture. The expression of CX3CR1 mRNA was significantly higher in DCOC than in MoOC. In DCOCs recovered by microdissection on day 4, confirmed significantly higher expression of CX3CR1 mRNA compared to MoOCs. Comparison of CX3CR1 mRNA expression with residing undifferentiated cells resulted in significantly higher expression in DCOCs, but not in MoOCs. Immunostaining on day 6 showed nuclear translocation of FOXM1 in both DCOCs and MoOCs. IL-6 or TNFα stimulation decreased viable cells in a concentration-dependent manner, with TNFα promoting MoOC differentiation and IL-6 promoting DCOC differentiation. <h3>Conclusion</h3> Compared to MoOCs, DCOCs expressed significantly higher CX3CR1 and FOXM1 from early stage of development specific to progenitor of inflammatory osteoclasts in in vivo. In addition nuclear translocation of FOXM1 suggested its role in gene regulation during OC differentiation. In addition, enhancement of DCOC differentiation by IL-6 is suggesting the usefulness of IL-6 inhibition for the pathophysiology of joint destruction in rheumatoid arthritis. <h3>References</h3> [1]Tetsuo Hasegawa,et al. Identification of a novel arthritis-associated osteoclast precursor macrophage regulated by FoxM1. Nat Immunol. 2019 Dec;20(12):1631-1643. [2]Silvia Marino,et al.Generation and culture of osteoclasts. Bonekey Rep.2014;3:570. [3]Keiichi Koizumi,et al.Role of CX3CL1/Fractalkine in Osteoclast Differentiation and Bone Resorption.J Immunol.2009 183(12):7825-7831. [4]Ibáñez, L. et al. Inflammatory osteoclasts prime TNFα-producing CD4+ T cells and express CX3CR1. J. Bone Miner. Res. 31, 1899–1908 (2016). <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.
AB0236 THE HAPTOGLOBIN 2-2 GENOTYPE IS ASSOCIATED WITH INCREASED RISK OF CARDIOVASCULAR DISEASE IN PATIENTS WITH RHEUMATOID ARTHRITIS: A CASE-CONTROL STUDY
Authors: C. Xu, L. W. Khin, H. Z. Tam, E. T. Koh, R. Dalan, K. P. Leong
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Traditional risk factors do not fully explain the increased risk of cardiovascular disease (CVD) in patients with rheumatoid arthritis (RA). [1] The Hp2-2 genotype is known to confer a lower anti-oxidant and higher inflammation effect when compared to the non Hp2-2 genotype. [2] <h3>Objectives</h3> This study aims to investigate the association of Hp genotype with CVD in patients with RA. <h3>Methods</h3> Sixty-nine with CVD cases and 207 gender and ethnicity matched control (without CVD) with allocation of 1:3, were retrieved from the Tan Tock Seng Hospital RA registry from 1 Jan 2000 to 31 Dec 2020. Hp genotype was determined using TaqMan-based real-time polymerase chain reaction (PCR). CVD was examined against demographics, clinical and laboratory variables in univariate models. Associations between Hp genotypes and CVD were analyzed using conditional logistic regression. All analysis was done using Stata version 16.1. <h3>Results</h3> The prevalence of Hp2-2 genotype was: Group 1 (CVD group): Chinese: 29/57, 50.9%, Indian: 5/5, 100%, and Malay 2/7, 28.6%; Group 2 (Control group): Chinese 80/171, 46.8%, Indian: 10/15, 66.7%, and Malay 11/21, 52.4%). CVD was significantly associated with age, disease duration, disease activity score 28 (DAS28), diabetes, hypertension, hyperlipidemia, Hp 2-2 allele, rheumatoid factor, cyclic citrullinated peptide (CCP), cumulative dose of prednisolone and methotrexate. Hp 2-2 genotype significantly associated with CVD outcomes in the logistic regression model adjusting for age, smoking status, DAS28, diabetes, hypertension, hyperlipidemia, and CCP (adjusted matched odds ratio: 1.13 (95% CI: 1.01 – 1.27); p = 0.033). <h3>Conclusion</h3> The Hp 2-2 genotype is associated with an increased risk of CVD in patients with RA in the Singapore multi-ethnic Asian cohort. Further epidemiological and mechanistic studies are warranted to understand the role of the Hp-genotype in rheumatoid arthritis. <h3>References</h3> [1] Agca R, Heslinga SC, Rollefstad S, Heslinga M, McInnes IB, Peters MJL, et al. EULAR recommendations for cardiovascular disease risk management in patients with rheumatoid arthritis and other forms of inflammatory joint disorders: 2015/2016 update. Annals of the Rheumatic Diseases. 2017;76(1):17-28. [2] Costacou T, Levy AP. Haptoglobin Genotype and Its Role in Diabetic Cardiovascular Disease. Journal of Cardiovascular Translational Research. 2012;5(4):423-35. <h3>Acknowledgements</h3> We thank Ms Amelia Lim Qiu Ru, and Ms Choong Ying Qi for the assistance with data collection. This work is supported by Tan Tock Seng Hospital FY2021 Pitch-for-Fund Program Grant (Grant ID: PFFP 21-08). <h3>Disclosure of Interests</h3> None Declared.
POS1159 GLUCOCORTICOID-SPARING EFFECT OF MEPOLIZUMAB: REAL LIFE EXPERIENCE IN A MONOCENTRIC COHORT OF PATIENTS AFFECTED BY EOSINOPHILIC GRANULOMATOSIS WITH POLYANGIITIS
Authors: S. Bertocchi, F. Regola, M. Taglietti, F. Franceschini, P. Toniati
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Oral glucocorticoids (GC) are the mainstay of treatment for eosinophilic granulomatosis with polyangiitis (EGPA) but chronic exposure to GC is associated with serious comorbidities. Mepolizumab (MEPO) demonstrated to be an efficacious treatment for EGPA in the randomized controlled MIRRA trial [1]. ACR guidelines suggest treating non-severe EGPA with MEPO associated with GC as first choice and adding MEPO in non-severe relapses occurred while receiving other immunosuppressants. There are insufficient data to support dosages and duration of GC treatment during MEPO treatment, although guidelines suggest prescribing the minimum effective dose to minimize GC toxicity [2]. <h3>Objectives</h3> The aim of the study was to evaluate the GC-sparing effect of MEPO in our cohort of patients affected by EGPA. <h3>Methods</h3> We enrolled 26 patients affected by EGPA according to MIRRA criteria and/or ACR criteria [1][3]. We compared cumulative GC dosage prescribed in the 6 months before beginning treatment with MEPO to the cumulative dosage prescribed in the 6 months after starting MEPO. We also analyse MEPO efficacy comparing median number of asthma attacks, BVAS and VDI. <h3>Results</h3> Twenty-six patients (M/F 16/10) affected by EGPA were diagnosed at a median age of 57 years (IQR 47-65) and started therapy with MEPO after a median disease duration of 6 (1.5-10) years. Overall clinical features of patients before MEPO starting, at MEPO starting (T0) and after 6 months of MEPO (T6) are described in Table 1a. At MEPO starting (T0), 24/26 (92.3%) were treated with GC and 13/26 (50%) were on treatment with other immunosuppressants (1 cyclosporine, 2 methotrexate, 3 mycophenolate, 7 azathioprine). The cumulative GC dosage administered to patients in the six months after MEPO starting was significant lower if compared with dosage in the prior six months. After MEPO starting, there was also a significant reduction of asthmatic flares number and BVAS score, with no increasing in VDI score (Table 1b and 1c). Eleven patients were treated with MEPO 300 mg monthly, and 15 with 100 mg monthly, with no statistically significant differences in clinical response. <h3>Conclusion</h3> In our cohort MEPO had a significant GC-sparing effect and significantly reduced asthma attacks and disease activity. <h3>References</h3> [1]Wechsler et al, 2017, NEJM [2]Chung et al, 2021, Arthritis Rheumatol [3]Masi et al, 1990, Arthritis Rheum <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.
AB0106 CAUSAL RELATIONSHIP BETWEEN IL-17 FAMILY MEMBERS AND THEIR RECEPTORS AND ANKYLOSING SPONDYLITIS: A TWO-SAMPLE MENDELIAN RANDOMIZATION STUDY
Authors: Y. X. Chen, X. Y. Guo, C. Wang, J. Q. Bai, J. Qiao, S. X. Zhang, P. F. He, Q. Yu
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Ankylosing spondylitis (AS) is an axial rheumatic and spinal disease based on autoimmune and genetic susceptibility that affects the sacroiliac joints and the spine<sup>[1]</sup>. Interleukin 17 (IL-17) as an inflammatory cytokine positively correlated with disease activity in AS patients<sup>[2]</sup>. However, the causal relationship between the IL-17 family and its receptors and AS is inconclusive. <h3>Objectives</h3> The aim of this study was to discover the casual association between the IL-17 family members with their receptors and AS. <h3>Methods</h3> To clarify the causal relationship between the IL-17 family members (and their receptors) and AS, we used two-sample Mendelian randomization (MR). We selected single-nucleotide polymorphisms (SNPs) from genome-wide association studies (GWAS) which included IL-17 family members and their receptors (N = 3301) and AS (Ncase = 968, Ncontrol = 336,191). Confounding factors were excluded, heterozygosity and lateral polymorphisms were examined and corrected. <h3>Results</h3> We found that IL-17RB level was significantly causally associated with AS (IVW OR=1.0007, 95%CI 1.0002~1.0011, P= 0.0020, Figure 1a). Sensitivity analysis also confirmed the absence of horizontal polymorphism (MR-Egger intercept = 6.5989×10<sup>-5</sup>, P = 0.5158, Figure 1b) and heterogeneity (IVW Q = 10.7388, Q_pval = 0.5514) that biased the causality. The leave-one-out sensitivity test showed that no single SNP strongly affected the causal relationship between IL-17RB and AS (Figure 1c). Furthermore, funnel plot symmetry suggests that our study fits the IV hypothesis(Figure 1d). However, our results show no significant causal relationship between AS and other IL-17 family members and their receptors. <h3>Conclusion</h3> Our results show that IL-17RB is a protective factor for AS. We offer a new insight into the drug targets of AS. <h3>References</h3> [1]El Maghraoui, A., Extra-articular manifestations of ankylosing spondylitis: prevalence, characteristics and therapeutic implications. <i>Eur J Intern Med</i><b>2011,</b><i>22</i> (6), 554-60. doi:10.1016/j.ejim.2011.06.006 [2]Zhang, X.; Yuan, Y.; Pan, Z.; Ma, Y.; Wu, M.; Yang, J.; Han, R.; Chen, M.; Hu, X.; Liu, R.; Sam, N. B.; Xu, S.; Pan, F., Elevated circulating IL-17 level is associated with inflammatory arthritis and disease activity: A meta-analysis. <i>Clin Chim Acta</i><b>2019,</b><i>496</i>, 76-83. doi:10.1016/j.cca.2019.06.026 <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.
POS0977 DEEP ANALYSIS OF SKIN MOLECULAR HETEROGENEITIES AND THEIR IMPLICATIONS ON THE PRECISE TREATMENT OF PATIENTS WITH PSORIASIS
Authors: L. L. Zheng, J. W. Hao, L. C. Zhang, J. Qiao, M. J. Chang, S. X. Zhang, X. Li
Journal: Annals of the Rheumatic Diseases (2023)

Background Psoriasis is a highly heterogeneous autoinflammatory disease [1] . Molecular and cellular characteristics of the patient skin are major determinants of clinical outcome for a given treatment [2] .Current disease heterogeneity has not been sufficiently translated to specific treatment option. Objectives We aimed to develop and validate a novel stratification scheme by integrating large-scale transcriptomic profiles to determine the heterogeneity of psoriasis, identify patient subtypes, and provide insights for designing stratified treatments. Methods We performed functional enrichment and network analysis of upregulated differentially expressed genes (DEGs) using microarray datasets of lesional and non-lesional skin samples from 250 patients with psoriasis. Unsupervised clustering methods were used to identify the skin subtypes [3] . Finally, the Xgboost classifier was constructed to predict the responses of stratified subtypes to commonly used biologics. Results Based on the 163 upregulated DEGs, the patients with psoriasis were categorized into three subtypes (subtypes Ased biologics. datasets of lesional and non-lesional skin samples from 250 patients with psoriasiselated pathways were markedly activated in subtype A, named immune activation. Contrastingly, subtype C, named stroma proliferation, was enriched in integrated stroma cells and tissue proliferation-related signaling pathways. Subtype B was modestly activated in all the signaling pathways. Notably, subtypes A and B presented good responses to methotrexate (MTX) and IL-12/23 inhibitors (ustekinumab) but inadequate responses to TNF-α inhibitors and IL-17A receptor (IL-17RA) inhibitors. In contrast, subtype C exhibited excellent responses to TNF-α inhibitors (etanercept) and IL-17RA inhibitors (brodalumab) but not MTX and IL-12/23 inhibitors. Conclusion Deep stratification based on skin heterogeneities was employed to categorize patients with psoriasis into three subtypes with distinct molecular and cellular signatures, which determined the clinical responses of different conventional therapies. References [1]Kim WB, Jerome D, Yeung J. Diagnosis and management of psoriasis . Can Fam Physician 2017; 63(4):278-285. [2]Armstrong AW, Read C. Pathophysiology, Clinical Presentation, and Treatment of Psoriasis: A Review . Jama 2020; 323(19):1945-1960. [3]Wilkerson MD, Hayes DN. ConsensusClusterPlus: a class discovery tool with confidence assessments and item tracking . Bioinformatics 2010; 26(12):1572-1573. Acknowledgements: NIL. Disclosure of Interests None Declared.